Part I Overview Information


Department of Health and Human Services

Issuing Organization
National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov)

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
This Program Announcement (PAR) is developed as an NIH roadmap initiative (http://nihroadmap.nih.gov). All NIH Institutes and Centers participate in roadmap initiatives. The PAR will be administered by the National Institute of Mental Health (NIMH) on behalf of the NIH.

Title: Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (X01)

Announcement Type
This is a reissue of PAR-05-147 that will expire with the issuance of this PAR. This PAR supercedes PAR-05-147 for the May 18, 2006 and new subsequent receipt dates. New applications require electronic submission through Grants.gov using SF424R&R forms instead of the SF424 forms that were previously used in PAR-05-147. Programmatic aspects of the original announcement remain the same.

Update: The following update relating to this announcement has been issued:

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines provided with this announcement in Grants.gov Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and should be started at least four weeks in advance of the planned submission. See Section IV.

Two steps are required for on time submission:

1) The application must be submitted to Grants.gov by 5:00 p.m. local time (of the applicant institution/organization) on the submission date (see “Key Dates” below).

2) Applicants must complete a verification step in the eRA Commons within two business days of notification from NIH. Note: Since email can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Commons.

Program Announcement (PA) Number: PAR-06-259

Catalog of Federal Domestic Assistance Number(s)
93.242


Key Dates (Revised Per NOT-RM-07-003)
Letters of Intent Receipt Date(s): Jan 26, 2007; May 26, 2007 and Sept 26, 2007.
Application Submission/Receipt Date(s): Feb 26, 2007; Jun 26, 2007 and Oct 26, 2007
Peer Review Date(s): April 2007; August 2007 and December 2007.
Council Review Date(s): September 2007; January 2008 and May 2008.
Earliest Anticipated Start Date(s): October 2007; February 2008 and June 2008.
Expiration Date: October 27, 2007

Key Dates (Orginal)
Release/Posted Date: March 24, 2006
Opening Date: April 18, 2006 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): April 20, 2006; Aug 16, 2006; Dec 20, 2006; Apr 20, 2007 and Aug 16, 2007
Application Submission Date(s): May 18, 2006; Sep 14, 2006; Jan 18, 2007; May 18, 2007 and Sep 14, 2007
Peer Review Date(s): Jul 2006; Nov 2006; Mar 2007; Jul 2007 and Nov 2007
Council Review Date(s): October 2006, January 2007; May 2007; October 2007 and January 2008.
Earliest Anticipated Start Date: November 2006; March 2007; July 2007; November 2007 and March 2008.
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: September 15, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

The National Institutes of Health (NIH) is committed to a major effort to broaden access to high-throughput screening (HTS) technologies, and the information produced by these approaches, for researchers in academia, government, and non-profit institutions. The public sector has not yet taken advantage of the considerable potential of HTS to advance the understanding of biology and disease mechanisms because access by academic scientists to automated screening facilities and diverse compound libraries is very limited. The NIH Molecular Libraries and Imaging Roadmap initiative (http://nihroadmap.nih.gov/molecularlibraries/index.asp ) has launched the Molecular Libraries Screening Centers Network (MLSCN) on June 15, 2005, which aims to enable the rapid transformation of new scientific knowledge into tangible benefits for public health. This effort will empower multi-disciplinary academic teams to discover small molecule tools that can be used in basic biological and biomedical studies. Descriptions of the ten network screening centers and their capabilities are available at http://nihroadmap.nih.gov/molecularlibraries/fundedresearch.asp.

The NIH wishes to enhance access to HTS capabilities for the academic community in order to speed the discovery of molecular research tools (e.g., ligands, imaging probes, and new activities of existing drugs) that will be available to the public sector. It is also anticipated that this MLSCN effort will catalyze scientific breakthroughs that will contribute to the identification of molecular entities or molecular classes that may accelerate the development of therapeutics by the private sector. Through this approach, NIH wishes to stimulate research in the following areas: 1) discovery of novel biological targets that can inform studies of cell function and disease mechanisms; 2) development, validation, and application of screening assays and disease models to evaluate the activity of novel small molecules; and 3) use of chemical genomic approaches to characterize the biology of genes of interest, cellular processes, and proteins associated with disease processes.

The MLSCN is a collaborative research network that is comprised of nine extramural centers and one NIH intramural screening center. The network of centers is capable of screening 100-200 assays adaptable to HTS annually. HTS assays will be selected for implementation in the MLSCN from those submitted by the research community in response to the Program Announcement “Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (MLSCN).” Each screening center will implement innovative HTS approaches to identify compounds that are active in target-based and phenotypic assays using 96-well, 384-well or 1536-well plate formats, as appropriate to the specific assay and screening platform.

As a national research resource, the MLSCN interfaces with other components of the Molecular Libraries Roadmap initiative, including the Molecular Libraries Small Molecule Repository (http://mlsmr.discoverypartners.com/MLSMR_HomePage ), PubChem (http://pubchem.ncbi.nlm.nih.gov ), and ongoing initiatives for cheminformatics and for technology development in the areas of assay development, chemical diversity, screening instrumentation, and algorithms for predicting biological activity of small molecules (see http://nihroadmap.nih.gov/molecularlibraries/grants.asp ). The Small Molecule Repository will acquire and maintain a collection of up to 500,000 compounds, from both commercial and academic sources, with well-known or unknown biological activities and diverse chemical structures. The repository will provide compounds to the screening centers for HTS. Within the MLSCN, HTS hits, the active compounds identified through initial screening, will be developed through optimization chemistry and further screening into useful bioactive probes that can be used by the scientific community to study molecular targets, cellular pathways, and potentially as starting points for drug development that will occur outside the MLSCN. The chemical structures of the compounds in the Small Molecule Repository, along with the related screening data, and assay protocols generated by the MLSCN will be deposited into a public database, PubChem. Information about the bioactive compounds will be made available to all researchers, who will be free to adapt them in biological and biomedical research studies. For funding opportunities supported by the Molecular Libraries Roadmap assay development initiatives, see website at http://nihroadmap.nih.gov/molecularlibraries/grants.asp

Objectives of the Project

The objective of this FOA is to invite HTS assay applications to support the Molecular Libraries Screening Centers Network (MLSCN). The goal of the MLSCN is to optimize and implement a variety of innovative biological, biophysical and cell-based assays for biological targets or processes for which there are limited selective and potent small molecule modulators available to the public. Applications are invited from investigators who have developed innovative assays for use both in basic research and in therapeutics development programs, and who are interested in having them used within the MLSCN to screen the repository library. The MLSCN intends to select approximately 100-200 assays per year for implementation within the ten screening centers.

Services Provided by the MLSCN

The MLSCN will provide the following services for those assays selected for implementation in this program.

1. Assay Implementation: The MLSCN will adapt, optimize and automate existing target-based and cell-based phenotypic assays obtained from the scientific community to 96-well, 384-well or 1536-well plate format as appropriate to the specific assay, screening approach, and level of throughput anticipated. The MLSCN will be capable of implementing assays using a variety of detection readouts such as absorbance, fluorescence, luminescence, scintillation proximity assay (SPA), fluorescence energy transfer (FRET), bioluminescence resonance energy transfer (BRET), biophysical readouts, and cell based imaging screens.

2. Compound Library: The Small Molecule Repository is in the process of expanding a compound collection of up to 500,000 compounds with known or unknown biological activities and diverse chemical structures, and it will maintain these compounds and distribute them to the MLSCN screening centers. The chemical structures of the compounds in the repository can be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pcsubstance&term=DPISMR[sourcename.

3. HTS Screening: The MLSCN will screen the repository compounds for biological activity in HTS assays to identify and confirm hits. Secondary assays, using a different readout, will be performed on initial hits in order to minimize false-positive results. Biological screening data will be deposited in PubChem (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pcassay).

4. Optimization Chemistry: The MLSCN will provide a moderate level of optimization chemistry capabilities to provide analogues of initial hit compounds to improve properties such as potency and solubility. Chemistry efforts are expected to include designing initial structure-activity relationships (SAR) and generating analogues around a confirmed hit.

5. HTS Informatics: The MLSCN will provide informatics support to track compounds, assays, and screening data. PubChem will support investigators with information for obtaining active compounds for their use in further research by identifying a source for purchase or synthesis of particular compounds. Any users of the data deposited into PubChem will be required to acknowledge the source of the data.

Guidance for HTS Assay Application

HTS is rapid screening of a large number of compounds in a biological assay. Since assays accepted by the MLSCN will be involved in high-throughput, robotic testing of compounds from the repository, the assays submitted should be adaptable to HTS with reasonable effort. It is anticipated that many of these assays will need to undergo further development to be usable in HTS formats, and such development will be accomplished through joint efforts between the submitter and the MLSCN screening center that is selected to implement the assay. Assay applications will be evaluated in terms of the following characteristics:

1. Readiness for or adaptability to HTS: HTS assays are primarily characterized by miniaturization and automation, and are usually conducted in microtiter plates, such as 96-well, 384-well or 1536-well plates. Assays submitted for HTS should be well established and characterized. If achievable, assays should have simple procedures readily adaptable to automation. Steps such as centrifugation, filtration and extraction should be avoided. Homogeneous, i.e. “mix and measure,” assays are preferable.

2. Assay performance and robustness: Performance characteristics of an assay should be suitable and reliable for automated HTS. Assays should be robust, reproducible and meet minimum statistical thresholds for robotic screening. Robustness is a measure of the capacity of the assay to remain unaffected by small changes in method parameters and provides an indication of its reliability during normal run conditions. The Z’-factor, a calculated parameter, is commonly used to quantify assay performance, and it accounts for both the signal-to-background and the amount of variability in the assay. Assays with Z’ parameters >0.5 are typically HTS compatible assays. The coefficient of variation (CV) determined from the entire sample and control wells of the microtiter plate should not exceed 10%. Reproducibility between plates and day-to-day experiments also provides useful information on how well the assay will perform.

3. Diversity of assay types: Assays developed for HTS can be roughly characterized as target-based or phenotypic assays. A biological target is a macromolecule or a set of macromolecules in a biochemical pathway. Phenotypic assays measure a signal which corresponds to a complex response such as cell survival, proliferation, localization of a protein, nuclear translocation etc. The molecular target is not assumed in a phenotypic assay.

The following are some examples of HTS assays: 1) target-based biochemical assays may include enzymatic assays (such as kinases, proteases and transferases), and receptor-ligand binding assays (such as those for G-protein coupled receptors (GPCRs), orphan GPCRs, ion channels, transporters, nuclear receptors, and new targets emerging from genetic and proteomic research in model systems and in human diseases; 2) cell-based assays could include functional assays, reporter gene assays and phenotypic assays for cellular processes and pathway analysis (e.g., viability assays for proliferation or apoptosis); 3) non-traditional targets of interest include transcription factors, nucleic acids, multimeric proteins, membrane proteins, and polymorphic gene products, and subcellular processes such as molecular trafficking and translocation, post-transcriptional editing or splicing of gene products, and protein or RNA stabilization; and 4) other assays of interest include those for metabolism, bioavailability, toxicity, and blood-brain barrier permeability.

To learn more about HTS assay development, please refer to the online comprehensive guidebook “Guidance for Assay Development and HTS” at http://www.ncgc.nih.gov/manual/toc.html. Additional resources include: the “ASSAY and Drug Development Technologies”, a peer-reviewed bimonthly journal that publishes articles, papers, and editorial commentary that emphasize early-stage screening techniques including assay design, target development, high throughput technologies and chemistry (http://www.liebertpub.com/publication.aspx?pub_id=118); and the Journal of Biomolecular Screening, the official Journal of the Society for Biomolecular Screening ( http://jbx.sagepub.com).

Material and Data Sharing

Submitting investigators will be required to provide necessary reagents such as cells expressing recombinant enzymes/proteins, primary and secondary antibodies, tagged peptide substrates, and available positive controls (e.g., a known inhibitor of the target). Investigators are expected to adopt uniform policies, such as data sharing, and procedures recommended by the MLSCN committee. All screening data and descriptions/protocols for assays optimized for HTS by the MLSCN will be deposited in PubChem immediately after they have been verified for accuracy. All data generated by the MLSCN will be freely available to the research community in a form that will support redisplay and reanalysis, so that maximal utility of this research resource will be realized. For the MLSCN Project Team Policy on Data Sharing and IP in the MLSCN Program, see http://www.nimh.nih.gov/dnbbs/datasharing-ip.pdf .

See details of NIH data sharing guidance http://grants1.nih.gov/grants/guide/notice-files/NOT-RM-04-014.html .

Project Oversight

As part of the larger Molecular Libraries Roadmap initiative, projects that are awarded under this PAR are subject to oversight and evaluation by each of the following entities.

MLSCN ASSAY ACCESS COMMITTEE. This NIH committee will evaluate assay proposals for scientific merit and feasibility for HTS. The Scientific Review Administrator (SRA) for this panel is an NIH review staff member, and the panel members will be primarily non-federal scientists (see the MLSCN Assay roster at http://www.nimh.nih.gov/grants/peerindex.cfm). Recommendations of the MLSCN Assay Access Committee will be communicated to the NIH Project Team and to the MLSCN Steering Committee.

MLSCN STEERING COMMITTEE. The steering committee for the overall MLSCN consists of the Director (PI) of each of the screening centers and the Small Molecule Repository, as well as NIH Program Managers and Science Officers, and will be the primary operational governing board of the MLSCN. The functions of this group include: 1) recommending the assignment and scheduling of assays and tasks, 2) developing guidelines to standardize the validation of screening data in different types of assays across centers; and 3) developing uniform procedures and policies for assay validation, data quality measures, assessment procedures, and annotation conventions for data depositions in PubChem.

NIH PROJECT TEAM. The NIH Project Team will serve as the governing body that coordinates and oversees the interaction of NIH with the centers and the MLSCN Steering Committee.

Section II. Award Information


1. Mechanism of Support

The FOA uses the NIH Resource Access award mechanism X01 for biomedical researchers to submit applications to obtain access to the MLSCN HTS and chemical optimization resources. Investigators do not need to request funds or personnel to utilize the Resource.

2. Funds Available

Through its funding of the MLSCN, NIH will support the costs of assay automation, screening and optimization chemistry (http://grants1.nih.gov/grants/guide/rfa-files/RFA-RM-04-017.html ). Applications received in response to this FOA will not receive any additional funds. A related Request for Applications is available to support early stage HTS assay development through the Molecular Libraries Roadmap ( http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-06-011.html).

The total number of X01s awarded will depend on the number of applications received, their relative scientific merit, and the general availability of funds for NIH Roadmap. The earliest possible start date for applications submitted in response to this program announcement is November, 2006.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the preliminary studies to support the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs

2. Cost Sharing or Matching

Cost sharing is not required. The most current Grants Policy Statement can be found at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

2. Other-Special Eligibility Criteria

There is no limit to the number of applications an applicant may submit under this announcement. One application can contain parallel screens for multiple related molecular targets or cellular systems within a screening plan.

Section IV. Application and Submission Information


To download an Application Package and Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

Project Directors/Principal Investigators (PD/PIs) should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organization/Institutional Registration in Grants.gov/Get Started

2) Organization/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the “Attachment” files may be useable for more than one FOA.

For further assistance contact GrantsInfo, Telephone 301-435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Tips and Tools for Navigating Electronic Submission” on the front page of “Electronic Submission of Grant Applications.”

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person

PHS398 Cover Page Supplement

PHS398 Research Plan
PHS 398 Checklist

Optional Components:
PHS398 Cover Letter File

2.A. General Instructions

Follow the instructions for completing the SF424 components found in the Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Ver2.doc) with the following special instructions below.

2.B. SF424 (R&R) Cover Component

This is a required component for any SF424 R&R-based application package. It contains all of the data elements found on the SF424 face page (which the X01 previously used in PAR-05-147). This form has an advantage over the SF424 face page in that it explicitly recognizes and collects data (in block 15) regarding the principal investigator. Applications solicited under the X01 mechanism will receive standard validation for data consistency, with the following exceptions:

16. Estimated Project Funding. Enter zero for lines a, b and c. Since the X01 (Resource Access Award) results in the award of resources NOT funds, any non-zero value will be treated as an ERROR. No budget forms will be used in the X01 submission.

2.C. SF424 Research & Related Other Project Information

1. Are Human Subjects Involved? Check “no”.

2. Are Vertebrate Animals Used? Check “no”. (Check “yes” only when applicable such as Zebrafish based assay).

6. Project Summary/Abstract. The Project Summary/Abstract ( i. e. “Description”) must state the application’s broad, long-term objectives and specific aims, making reference to the health relatedness of the project. Describe concisely the research design and methods for achieving the stated goals.

Attach Project Summary/ Abstract file in line 6, and the attachment must be a PDF format.

7. Project Narrative. Using no more than two or three sentences, describe the relevance of this project to public health or to one or more disease areas. Attach The Project Narrative file in PDF format in line 7.

A separate Research Plan component is required for NIH and other PHS agencies applications.

9. Facilities & Other Resources. Describe only those resources that are directly applicable to the proposed work. Provide any information describing the Other Resources available to the project and the extent to which they would be available to the project. This information is used to assess the capability of the organizational resources available to perform secondary assays, low-throughput screening of chemical analogs of hits developed by the MLSCN center, or chemical optimization efforts after the high throughput screening at the MLSCN. If appropriate, indicate previous interactions with screening centers in the MLSCN.

10. Equipment. Not applicable. Do not include an attachment here.

11. Other Attachments. If required, biosafety information for the biological material should be attached separately in line 11.

2.D. Senior/Key Person Profile(s) Component

Provide a biographical sketch for the Senior/Key Person. Recommended information includes: Education and Training, Research and Professional Experience, Collaborators and Affiliations (for conflicts of interest), Publications and Synergistic Activities. Save the information in a single PDF file and attach by clicking Add Attachment. Biographical sketches should follow the format described below.

NIH and Other PHS Agencies Instructions for a Biographical Sketch

Use the sample format on the Biographical Sketch Format Page http://grants.nih.gov/grants/funding/424/SF424R-R_biosketch.doc to prepare this section for all grant applications. Include biographical sketches for all Senior/Key Personnel. The Biographical Sketch may not exceed four pages per person. This 4-page limit includes the table at the top of the first page.

If the individual is registered in the eRA Commons, include the assigned Commons User Name in the “Credential” field. For principal investigators, this data item is required.

2.E. PHS398 Cover Page Supplement

2. Human Subjects. Check “no” to both the Clinical Trial and Agency-Defined Phase III Clinical Trial questions.

4. Human Embryonic Stem Cells. Check “no”. (Check “yes” only when applicable).

2.F. PHS398 Research PlanThe following section contains the specific instructions for completing the research plan for X01 applications. Page limitation for Research Plan: 10 pages single-spaced (excluding appendices).

This form allows the attachment of the various sections of the standard research plan. This form collects each major section separately so that bookmarks and table-of-contents can be automatically generated for each section, by the NIH software that downloads, validates, and generates a grant image using the data received from Grants.gov. The PHS 398 Research Plan includes:

2. Specific Aims: describe a rational for the biological target or phenotype of the HTS and future plan for the use of the biological data or small molecule hits in a follow-up research program, either biological research or therapeutics development.

3. Background and Significance: describe the biological significance of the target or phenotype and potential impact of biological data and small molecule probes derived from the HTS assay on the scientific field of study.

4. Preliminary Studies: provide data and information on assay performance, quality controls, responses to pharmacological standards or other control conditions, feasibility for miniaturization and automation for HTS, tolerance to the effect of DMSO, reagent availability, reagent stability, etc.

5. Research Design & Methods:

Primary assay: provide a detailed assay procedure for the primary assay, i.e. assay performed in a testing scheme to identify biologically active chemical entities in a screening mode. Include sources of specific materials such as purified or crude biochemical reagents or cells and the microtiter plate well density (e.g., 96-, 384- or 1536-well) and plate composition (e.g., clear bottom black or clear bottom polystyrene, etc.). Specify reagents, software, and instrumentation used to measure response or output. (e.g. Fluorescence polarization or Radiometric counting).
The proposed assay should demonstrate highly robust and reproducible behavior in a 96-well or higher density format (e.g., 384- or 1536-well plates). Generally, the assay protocol should demonstrate: 1) a signal of sufficient intensity that it can be easily measured from a microtitre plate in low volume, 2) a signal-to-background ratio of at least 5 and a coefficient of variation (CV) below 10% determined from measurements across the entire plate (these factors are typically expressed as the statistical parameter, Z', which has an acceptable lower limit of 0.5), 3) reproducible, dose-dependent responses to pharmacological standards or other control conditions, 4) tolerance to the effect of DMSO at 0.1-1%. Between-plate and day-to-day variations also provide useful information on how well the assay will perform, as will the determination of reagent stability to storage and assay conditions. The assay plan should include demonstration of selectivity and reproducibility of response to a small but diverse collection of at least several hundred compounds, such as a collection of FDA approved drugs or other bioactive molecules.
Cost estimation: estimate the costs of reagents that are commercially available. These costs should be calculated for a single well of a 96-well plate assuming an assay volume of 200 ul.
Secondary confirmatory assay: provide an available secondary screening assay to confirm hits and eliminate false positives. This secondary assay should use a different readout than the primary assay. These assays also include selectivity assays that employed to elucidate the specificity of biologically active chemical entities towards a set of closely related targets. Counter screening assays should also be provided if available.
14. Resource Sharing plan: in the case of the X01, describe material(s) to be provided to screening center. Submitting investigators will be required to provide necessary reagents such as cells expressing recombinant enzymes/proteins, primary and secondary antibodies, tagged peptide substrates, and available positive controls (e.g. a known inhibitor of the target). Indicate if any reagents are proprietary and if so, if there are Material Transfer Agreements in place to use the proprietary reagents within the MLSCN if the assay is selected for implementation.

15. Appendix: up to two significant publications or achievements may be included in the appendix.(See NOT-OD-06-051)

2.G. PHS 398 Cover Letter File

PHS 398 Cover Letter File: Attach a letter agreeing to allow the X01 application to be shared with the MLSCN Steering Committee members. The letter should be brief and include the title of the application. The information in this application will be kept confidential.

The MLSCN Steering Committee, which consists of the Directors of the ten screening centers within the network, the Director of the Small Molecule Repository, and NIH staff, will develop a plan for distributing each HTS assay to a specific screening center based on existing capacity and expertise of each center as well as information such as assay target, cost, workload, detection system, etc. The MLSCN Steering Committee members will need to review the information in your application in order to make assay assignments to individual centers. No decision regarding the final assay assignment will be made without this letter of agreement.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Proposed research should provide a unique research opportunity not available in the U.S.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review and Anticipated Start Dates

Letters of Intent Receipt Date(s): Jan 26, 2007; May 26, 2007 and Sept 26, 2007.
Application Submission/Receipt Date(s): Feb 26, 2007; Jun 26, 2007 and Oct 26, 2007
Peer Review Date(s): April 2007; August 2007 and December 2007.
Council Review Date(s): September 2007; January 2008 and May 2008.
Earliest Anticipated Start Date(s): October 2007; February 2008 and June 2008.

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent via email by the date listed at the beginning of this document.

The letter of intent should be sent to:

Ingrid Li, Ph.D.
Molecular Libraries Assay Access Project Team
NIH Molecular Libraries & Imaging Roadmap
National Institute of Mental Health/NIH/DHHS
6001 Executive Boulevard, Room 7185, MSC 9641
Bethesda, MD 20892-9641
Rockville, MD 20852-9641 (for express/courier service)
Telephone: (301) 443-5288
FAX: (301) 402-4740
Email: ili1@mail.nih.gov

To permit expedited review of X01 applications, PD/PIs are asked to notify the NIMH Referral Office by email when the application has been submitted through Grants.gov.

NIMH Referral Office
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD 20892-9609
Telephone: (301) 443-3367
FAX: (301) 443-4720
Email: NIMHReferral@mail.nih.gov

3.B. Electronic Transmission of an Application to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically.
PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted to Grants.gov on or after the opening date and must be submitted no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission date(s). (See Section IV.3.A. IV.3.A. for all dates.) If an application is not submitted by the submission date(s) and time, the application may be delayed in the review process or not reviewed.

Upon receipt, applications will be transferred from Grants.gov to the NIH Electronic Research Administration process for validation. Both the PD/PI and the Signing Official for the organization must verify the submission via Commons within two (2) business days of notification of the NIH validation.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

6. Other Submission Requirements

Resubmissions (formerly called revised/amended) applications are not allowed. Submit every application as a new application (or as a “changed/corrected” application, if needed because of submission errors).

PIs should submit a letter with their application, agreeing to allow their application to be shared with the MLSCN Steering Committee members. The information in their applications will be kept confidential. This letter should be appended to Optional Components: PHS398 Cover Letter File in the application package.

The NIH requires the PD/PI to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Tips and Tools for Navigating Electronic Submission” on the front page of “Electronic Submission of Grant Applications.”

Plan for Sharing Research Data

Data Sharing Plan:
The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. The presence of a data sharing plan will be part of the terms and conditions of the award. Program staff of the funding organization and NIH Project Team staff will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

Since the inception of the ML Roadmap, NIH has emphasized that in order to yield the maximum benefit, all physical and intellectual research resources should be publicly available. There are strong scientific arguments supporting this position. Small molecule probes that selectively interact with biological targets are key research tools for understanding the functions of proteins and for elucidating biological pathways. A collection of such probes that would allow the comprehensive study of all of the proteins and other gene products encoded by the human genome would be an invaluable contribution to biomedical research. It will take the combined efforts of researchers in the public and private sectors many years of using small molecule probes to completely characterize the biology of genes and proteins in health and disease, and then to use that information to develop approaches that will improve public health. Clearly, the open sharing of data, research tools, and resources will lead more rapidly to the identification and validation of novel targets for drug discovery, and will facilitate the rapid development of therapeutics by both the private and public sectors, with resulting benefits to public health, especially for rare or marginalized disorders.

The willingness to comply with the NIH data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Guidance for Community Resources. The following data and materials generated or developed through the ML Roadmap initiative are expected to be community resources: (1) primary data from HTS and from secondary screens; (2) protocols for assays implemented in the MLSCN; (3) the chemical structures of compounds tested in the MLSCN; and (4) the optimization chemistry protocols for probe development conducted within the MLSCN centers. In keeping with this approach, NIH expects that (1) all assays and assay protocols submitted to the NIH under this FOA, and (2) biological screening data derived from implementing the assays in the MLSCN will be made readily available and accessible, consistent with other facets of the ML Roadmap http://grants.nih.gov/grants/guide/notice-files/NOT-RM-04-014.html .

It is NIH's understanding that the utility of the resources and data generated by the ML initiative will be maximized if they are treated as community resources and made broadly available, consistent with achieving the goals of the ML Roadmap. While NIH recognizes that under the Bayh-Dole Act, awardees have the right to elect title to subject inventions and seek appropriate IP protection, the data sharing and IP plans should take all of the above considerations into account. Applicants should provide clear explanations and rationales for their plans, especially for any proposed plan that involves principles differing from those described in this FOA.

A separate component of the IP plan should address any other data and resources that are expected to be generated by the grantees under this FOA. NIH encourages applicants to consider inclusion of "non-assert" language in IP plans for all potentially patentable inventions to ensure that, while an institution might apply for a patent on an invention, the institution would not attempt to enforce that patent against organizations utilizing the technology for research purposes.

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131 ). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization and by NIH Project Team staff when making recommendations about selecting assays for implementation within the MLSCN.

Submitting investigators will be required to provide necessary reagents such as cells expressing recombinant enzymes/proteins, primary and secondary antibodies, tagged peptide substrates, and available positive controls (e.g. a known inhibitor of the target).

Submitting investigators and MLSCN Centers will be expected to use an unmodified version of the Material Transfer Agreement (MTA) approved by the MLSCN Steering Committee for transfer of assays and materials to the individual MLSCN Centers (http://www.nimh.nih.gov/dnbbs/mta_10_31_2005.pdf).

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete will be evaluated for scientific and technical merit by an appropriate review group convened by NIMH in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

The following will be considered in making selection decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed HTS assay will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or practice be advanced? Is this assay for a novel biological target or cellular process? Is there no known small molecule modulator for this biological target available? Is there a need for better small molecule modulators against the target? Is this class of target extensively investigated? Is there an adequate plan for evaluating the activities of the compounds identified in a high throughput screen, e.g., in secondary screens and functional assays? Are there important and well-defined goals for the use of small molecule compounds identified with the proposed assay, either as research tools or for therapeutics development?

Approach. Is the assay well established and ready for HTS? Is the assay pharmacologically validated? Is there sufficient preliminary data for assay validation? Is there an assay performance parameter calculated, such as Z-factor? Is the assay readily adaptable by screening centers to an HTS format that is primarily characterized by miniaturization and automation? Is the assay feasible and reproducible, and does it and meet minimum statistical thresholds for robotic screening? Is there an adequate plan for assay reagents? Are the assay reagents readily available from the applicant (s) if reagents can not be commercially supplied? Is there an adequate plan for secondary assays to evaluate active compounds identified in the primary assays?

Innovation. Is the assay development project original and innovative? For example: Does the assay challenge existing paradigms or practice; address an innovative hypothesis or barrier to progress in the field of HTS? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators. Are the investigators appropriately trained and sufficiently knowledgeable about the target and area of science to support the collaborative screening effort and capable of advancing active compounds identified by the MLSCN? Are the investigators reasonably knowledgeable and experienced about assay development and the process of screening compounds library?

Environment. Does the scientific environment of the applicant (s) contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. See item 6 of the Research Plan component of the SF424 (R&R).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under item 11 of the Research Plan component of the SF424 (R&R) should be addressed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Assay Review and Selection: The following is the anticipated process for assay review and selection:

Assay Access Review Committee (SEP): Evaluate assay proposals for scientific merit and feasibility for HTS. The Scientific Review Administrator (SRA) for this panel will be a NIH review staff member, and the panel members will be primarily non-federal scientists. Recommendations of the Assay Access Committee will be communicated to the NIH MLSCN Project Team and to the MLSCN Steering Committee.

NIH MLSCN Project Team: Review summary statements and develop a balanced portfolio that is consistent with NIH-wide programmatic priorities. The list of assay proposals will be presented to the MLSCN Steering Committee for implementation within the screening centers network. Review the recommendations of the MLSCN Steering Committee regarding the choice and distribution of assays to specific centers and make final assignments of these assays to specific centers and give final approval for assay assignments to individual centers.

MLSCN Steering Committee: Review HTS assay proposals selected by NIH project team and develop a plan for distribution of assays to specific centers within the screening centers network based on the NIH Project Team's prioritization of assays acceptable for implementation, and information about existing capacity and expertise of each center such as assay target, cost, workload, detection system, etc.

Budget: Not applicable

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. The presence of a data sharing plan will be part of the terms and conditions of the award. Program staff of the funding organization and NIH Project Team staff will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant.

Submitting investigators will be required to indicate whether or not they have Material Transfer Agreements or Sponsored Research Agreements in place to use patented technology or assay reagents proposed in this application for non-commercial, research purposes. Investigators will be asked to provide documentation prior to assay being selected for implementation within the MLSCN.

3. Anticipated Announcement and Award Dates

Not applicable

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her peer review results and Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for selection, NIH will request the execution of the MLSCN Material Transfer Agreement (MTA) i.e. signed by the institution of the assay provider and a screening center as recipient.

The Principal Investigator who submitted the assay proposal will be notified by NIH staff if the assay has been selected for implementation in a specific MLSCN center.

2. Administrative and National Policy Requirements

Not applicable

3. Reporting

Not applicable

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and X01 application submission issues:

1. Scientific/Research Contacts:

Ingrid Li, Ph.D.
Molecular Libraries Assay Access Team
National Institute of Mental Health/NIH/DHHS
6001 Executive Boulevard, Room 7185, MSC 9641
Bethesda, MD 20892-9641
Rockville, MD 20852-9641 (for express/courier service)
Telephone: (301) 443-5288
FAX: (301) 402-4740
Email: ili1@mail.nih.gov

2. Peer Review Contacts:

Yong Yao, Ph.D.
NIH Molecular Libraries & Imaging Roadmap
Scientific Review Branch
National Institute of Mental Health/NIH/DHHS
6001 Executive Boulevard, Room 6149, MSC 9608
Bethesda, MD 20892-9608 (20852 for overnight couriers)
Telephone: (301) 496-9223
FAX: (301) 402-0182
Email: yyao@mail.nih.gov

3. X01 Submission Contacts:

John Grossi
Scientific Program Analyst
National Institute of Mental Health
6001 Executive Boulevard, Room 7185, MSC 9641
Bethesda, MD 20892-9641
Rockville, MD 20852-9641 (for express/courier service)
Telephone: (301) 443-5288
Email: GrossiJ@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://PublicAccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_manual.htm).

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR Website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:

This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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